There are a number of clinical situations where there is a need to re-establish or improve blood flow to a compromised or damaged tissue or organ. Often, the introduction of a new conduit vessel, either natural or artificial, upstream of an affected tissue or organ is sufficient to re-establish blood flow and relieve the symptoms exhibited by the affected tissue or organ. However, in situations where the replacement of an upstream, diseased conduit vessel does not resolve the condition, such as ischemia, it is necessary to regenerate the vascular supply within the tissue or organ. In these situations, the goal is thus to expand an existing vascular bed, especially the downstream vasculature, as a means to provide alternate and/or additional avenues for tissue or organ perfusion. In this regard, engineered tissue constructs offer promise to facilitate tissue healing and/or the replacement of compromised or damaged tissues and organs.
Current tissue engineering strategies, however, are hampered by the inability to pre-build a vasculature within the engineered construct. Indeed, the success of any tissue-engineered construct is highly dependent on the presence of a functional, invested vasculature within the construct as well as the ability to quickly perfuse the tissue construct once it is implanted into a subject. Any tissue construct greater in dimension than a few millimeters is too large for oxygen and nutrients to efficiently diffuse into the construct cells from the external environment and the surrounding host tissue. As such, the ability to grow and develop a vascular network within the construct is important for not only in vitro tissue construction, but also for in vivo vascular regeneration.
Existing strategies for building microvessels in vitro have involved a “de novo” approach in which freshly isolated or cultured vascular cells are placed within a scaffold, such as one formed by drilling channels into collagen sponges, by polymerizing collagen around metal or polymeric mandrels, or by utilizing polymer grafts. The vascular tubes that are formed by these microvascular constructs are capable of progressing into true microvessels and microvessel networks, but only when they are implanted into a living host. Alternative methods for building microvessels in vitro have employed isolated microvessel segments instead of cultured vascular cells, and have embedded these segments in a three-dimensional collagen matrix. In these later approaches, no further manipulation or addition of factors, such as growth factors or morphogens, is necessary to produce a new microvasculature network. However, the bioreactors that these three-dimensional constructs are produced within fail to provide sufficient perfusion paths through the constructs such that flow through the construct is maintained and the microvessels segments subsequently propagate into an organized and functional network of microvessels.
In any event, known methods and devices for building vessels in vitro are only capable of building microvessels within a preformed scaffold or are only capable of building a microvascular network that lacks organized perfusion paths within the construct itself. Furthermore, the known methods and devices for building vessels have only focused on building a collection of microvessels and have not sufficiently addressed how to build an organized network of microvessels such that a particular construct can then be implanted into an existing tissue and readily perfused, which is of great importance in treating compromised or damaged tissues or organs.